DIFFERENCES IN ARYLALKYLAMINE N-ACETYLTRANSFERASE ACTIVITY BETWEEN INFLAMMATORY DISEASE-SUSCEPTIBLE LEWIS AND DISEASE-RESISTANT FISCHER RATS

Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred str ains characterized, respectively, by susceptibility and resistance to inflammatory disease. The susceptibility of LEW/N rats to inflammation has been associated with deficient corticotropin-releasing hormone (C RH), ACTH, and corticosterone responses to inflammatory stimuli, speci fically attributed to a global impairment in hypothalamic CRH neuron f unction. In contrast to the LEW/N rats, F344/N rats demonstrate an int act hypothalamic-pituitary-adrenal (HPA) axis. Melatonin, a neurohormo ne initially isolated in the pineal gland,. has been implicated with i nhibition of the HPA axis. To investigate melatonin synthesis and secr etion in LEW/N and F344/N rats, we examined the diurnal activity of pi neal arylalkylamine N-acetyltransferase (NAT1), the rate-limiting enzy me in melatonin biosynthesis, which demonstrates circadian rhythmicity , as well as the diurnal levels of serum melatonin, in both strains. A rylamine N-acetyltransferase (NAT2), a related enzyme activity, though t not to be regulated in a circadian manner, was examined as a control of NAT1 activity. Pineal NAT1 activity peak was observed later and re ached significantly higher levels in LEW/N than in F344/N rats. Serum melatonin levels reflected the circadian pattern of the NAT1 activity, without, however, showing any quantitative differences between the tw o strains. Time-course of pineal NAT1 activity response to beta-adrene rgic stimulation was parallel in the two rat strains, whereas the magn itude of the response was greater in LEW/N than in F344/N rats. No cir cadian or major quantitative differences in NAT2 activity were found b etween the two strains. Size-exclusion HPLC chromatograms of NAT1 acti vity revealed similar patterns in both rat strains. These findings dem onstrate a difference in the circadian and beta-adrenergic-stimulated regulation of melatonin synthesis in the two rat strains.